18-01-22 - Sarcomere Structure Flashcards
Learning Outcomes
- Describe the organisation and roles of the main proteins located within the sarcomere
- Explain the interaction of myosin and actin in sarcomere shortening
- Explain the role of regulatory proteins troponin and tropomyosin
- Describe events occurring at the neuromuscular junction
- Briefly describe the innervation of skeletal muscle fibres and relationship between the transverse ‘T’ tubules and sarcoplasmic reticulum
Describe the 3 stages of embryonic muscle development?
What are satellite cells?
Where are they found? What is their role?
• Stages of embryonic muscle development:
1) Embryonic mesoderm cells called myoblasts undergo cell division in order to increase number and enlarge
2) Several myoblasts fuse together to form a myotube
3) Myotube matures into skeletal muscle fibre
• Satellite cells are mononucleated cells
• They are found wedged between the basement membrane and plasma membrane of the muscle fibre
• Satellite cells act as stem cells and are responsible for the further growth and development of skeletal muscles
What are sarcomeres?
What are myofibrils made of?
What are they responsible for?
What forms the boundaries between sarcomeres?
What are the 4 supporting proteins of sarcomeres responsible for maintaining structure?
What are the roles of each?
What can occur if there are mutations in the dystrophin gene?
What do mutations cause?
- Sarcomeres are the functional units of myofibrils
- Myofibrils are composed of overlapping thick (myosin) and thin (actin) myofilaments organised into distinct units called sarcomeres
- Myosin and actin are contractile proteins
- They are responsible for the contraction of muscles
- Z disks form the boundaries between sarcomeres
• 4 supporting proteins of sarcomeres responsible for maintaining structure:
1) Α-actinin
• Binds to actin and tethers it to Z discs
2) Titin
• Binds myosin and tethers it to the m lines and z discs
• Responsible for maintaining recoil of muscles after contraction
3) Nebulin
• Binds actin and holds it in place with I band
4) Dystrophin
• Binds actin and tethers it to the I band
• Also found on the outer myofibrils of cells where it tethers them to the extracellular matrix via the cell membrane
• The dystrophin gene is the largest in the genome, and if there are mutations in the introns and exons of the gene, it can lead to muscular dystrophy (weak muscles), with the most common being Duchenne’s muscular dystrophy
• Mutations can cause weaker forms or less dystrophin to be produced
• This can cause muscle to be replaced with connective tissue, leading to weaker muscles
What is the A band of the sarcomere made from?
What does the I band consist of?
What does I and A stand for?
What does the M line consist of?
- The A band of sarcomeres is predominantly made from thick filaments (myosin - dark area), with a bit of an overlap with actin at the edges
- The I band incorporates part of 2 sarcomeres, with the z disk as the boundary
- The I band contains thin filaments (actin) only
- The I band is the Isotropic band and the A band is the anisotropic band
- The M line consists of thick filaments linked by accessory proteins
What is the length of the A and I bands at rest?
What occurs during contraction?
What happens to the length of the A and I bands?
- At rest, the A and I bands are roughly similar length
- During contraction, the myosin binds actin, pulling inwards, shortening the sarcomere, which makes the Z discs move closer together
- The I band reduces in size
- The A band remains the same width, consisting of greater actin and myosin overlap
What does myosin consist of?
What are the 3 parts myosin-2 consists of?
- Myosin consists of 300-400 myosin-2 molecules, which are specifically designed for the contraction of muscle
- This forms a thick filament with globular heads protruding
• Each myosin-2 molecule consists of:
1) 2 intertwined heavy chains (MHC), each with globular heads
2) 2 essential light chains (MLC-1), which stabilises the myosin head
3) 2 regulatory light chains (MLC-2), which regulates the ATPase activity of myosin
What does actin consist of?
What are the 2 regulatory proteins linked to actin?
What is the role of tropomyosin?
What are the 3 different forms of Troponin?
What is the role of each?
- Actin consists of 2 intertwined α-helical chains of F actin
- The 2 regulatory proteins linked to actin and Tropomyosin and Troponin
- Tropomyosin prevents myosin binding to actin while in a relaxed state (no neuronal signal, no calcium, no ATP) by covering myosin binding sites
• 3 forms of Troponin:
1) TnC – binds Ca2+
2) TnT – Tropomyosin
3) Tnl – binds actin (inhibits contraction
Describe the 16 steps of muscle contraction.
What is the role of calcium in this process?
1) Action potential travels down the motor neuron
2) The motor neuron splits into end plate boutons that attach to myofibers, so when an action potential arrives, it can spread through all the myofibers an generate synchronous contraction
3) Voltage gated calcium channels open, and influx of Ca2+ initiates vesicles containing acetylcholine to fuse with the pre-synaptic membrane at the neuromuscular junction
4) The acetylcholine is released into the synaptic cleft
5) Each attach to Nicotinic Ach receptors (nAchR) in the post-synaptic sarcolemma (muscle cell plasma membrane) at the motor end plate
6) Acetylcholinesterase rapidly breaks down Ach in the synaptic cleft
7) The fusion to these receptors causes Na+ sodium channels in the sarcolemma to open, resulting in a wave of depolarisation across the surface of the muscle cell called the motor end plate potential
8) The transverse T-tubules, which are invagination of the sarcolemma, transmit this electrical impulse deep into the cell structure
9) The t-tubules are closely associated with the sarcoplasmic reticulum, and stimulates it to release Ca2+ into the muscle cell
10) Ca2+ binds to TnC, which causes a conformational change in TnI and TnT, resulting in tropomyosin revealing myosin binding sites on actin
11) When ATP is present, it attaches to the myosin head, reverting the myosin back to its low energy state, causing It to detach from the thin actin filament (cross-bridge detachment)
12) ATP Is hydrolysed to ADP and Pi by the myosin head, causing it to be cocked into its high energy position
13) The energised myosin head can then bind to the actin myofilament, forming a cross bridge
14) Then there is the power (working) stroke, where ADP and Pi are release and the myosin head pivots and bends, changing to its bent low-energy state
15) This results in the actin filament being pulled towards the m-line
16) The sarcomeres then shorten, and the muscle contracts
• Calcium couples (converts) the electrical stimulation into mechanical contraction, which is known as the excitation-contraction coupling
What is the sarcoplasmic reticulum?
What is the role of the SR?
What is the role of triads?
- The sarcoplasmic reticulum is an elaborate smooth endoplasmic reticulum
- It is a vast network of interconnecting tubules surrounding each myofibril, allowing them to contract in unison
- The sarcoplasmic reticulum stores calcium, and releases it upon the initiation of contraction
- Triads are regions where there is a t-tubule sandwiches between 2 sections of sarcoplasmic reticulum
- Like Calcium, triads couple (converts) the electrical stimulation into mechanical contraction, which is known as the excitation-contraction coupling
What occurs after contraction?
What happens to the Ca2+ in the sarcoplasmic reticulum?
What is responsible for this?
What does this generate?
How does the movement of Calcium after contraction differ between skeletal, cardiac and smooth muscle?
- After contraction, the action potential stops
- Ca2+ Is pumped back into the SR via active transport through the Sarco-endoplasmic reticulum calcium ATPase (SERCA)
- Within the SR, calsequesterin and calreticulin are major Ca2+ binding proteins in skeletal muscle, located primarily at the triad junction
- This generates up to 10,000 times for Calcium in the SR than the sarcoplasm, creating a massive concentration gradient calcium can flow down during the next contraction
- In cardiac and smooth muscle, calcium may also be transported extracellularly via symporters, but generally in skeletal muscle, it is pumped back into the SR
What is a muscle contraction summary?
